Studies in this proposal are designed to examine the relative contributions of disordered respiratory muscle function, abnormal lung mechanics and decreased drive to breathing to the development of respiratory failure in patients with chronic airway obstruction (C.A.O.). As indicated by Campbell in his recent monograph on the respiratory muscles, surprisingly little is known about respiratory muscle function in these patients. The aim of Project I is to examine the action of respiratory muscles during quiet breathing and increased levels of ventilation by relation measurements of ribcage and abdominal volume displacements (magnetometers) to pleural and abdominal pressure changes (esophageal and gastric balloons). In Project II the role of paradoxical thoraco-abdominal movements in the development of nocturnal hypoxemia will be examined. We suspect that paradoxical motion occurs during REM sleep (due to inhibition of intercostal muscle spindles yields ribcage instability) and contributes to alveolar hypoventilation and worsening V/Q relationships that frequently occur in patients with C.A.O. We will monitor sleep state (EEG), ribcage and abdominal motion (magnetometers), drive to breathing (diaphragm EMG) and arterial blood gases (oximetry and blood samples) during sleep. The degree of blood gas disturbance will be related to responsiveness to CO2 and hypoxia when awake. Project III will examine the contributions of worsening airway obstruction, muscle weakness, paradoxical thoraco-abdominal motion and decreased drive to breathing to the progression of acute-on-chronic respiratory failure. Conservative interventions (He/O2 gas mixtures, continuous positive airway pressure, respiratory stimulants) will be evaluated once the mechanisms have been identified.